Does electrophysical agents work for cellulite treatment? a systematic review of clinical trials.

Cellulite, a perceived alteration in skin topography, is predominantly found in adipose tissue-rich body regions such as the hips, buttocks, thighs, and abdomen. Contrary to common belief, the etiology and pathophysiology of cellulite are not well-established or universally agreed upon. This lack of understanding about the actual etiology of cellulite directly influences the selection of suitable treatments that can address both the aesthetic and inflammatory aspects of the condition. Various treatment methods, including electrophysical agents like electric currents, radiofrequency, ultrasound, and photobiomodulation, have been tested. However, the questionable methodological quality of many studies complicates the determination of effective treatments for cellulite. In this study, we conducted a systematic review of clinical studies that utilized electrophysical agents in cellulite treatment. METHODS: We employed the PICO (population, intervention, control, and outcome) process to develop our search strategy and establish inclusion/exclusion criteria. We searched five databases: Medline, Central, Scopus, Lilacs, and PEDro, for studies conducted between 2001 and July 2021 that involved cellulite treatment with electrophysical agents. To ensure systematicity and guide study selection, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. RESULTS: Our initial search yielded 556 articles: 379 from Medline, 159 from Central, and 18 from Lilacs. After applying our inclusion criteria, only 32 studies remained. Of these, only two (6.2%) were evaluated as having strong and good methodology via the QualSyst tool. CONCLUSIONS: Our findings indicate that the quality of evidence from clinical studies on the use of electrophysical agents for cellulite treatment remains subpar. Further studies with robust experimental designs and more precise assessment techniques are necessary. While our study does not refute the effectiveness of the techniques used for cellulite treatment, it underscores the need for additional well-designed trials.

Effects of photobiomodulation on pain, lactate and muscle performance (ROM, torque, and EMG parameters) of paretic upper limb in patients with post-stroke spastic hemiparesis-a randomized controlled clinical trial.

The objective of the study was to investigate the impact of photobiomodulation (PBM) on the paretic upper limb in post-stroke patients with spastic hemiparesis and to understand the potential of PBM as a long-term non-invasive therapy for reducing the side effects caused by spasticity in the hemiparetic upper limb after a stroke. This is a double-blind randomized clinical trial constituted of 27 participants, being Control group (CG = 12 healthy individuals) and PBM group (PBMG = 15 post-stroke individuals). In the CG, the baseline blood lactate (BL) was evaluated, followed by the evaluation of the IC torque of the biceps and triceps muscles, with the isokinetic dynamometer associated with surface electromyography (EMG) and, subsequently, a new measurement of BL. The PBMG received 10 sessions of treatment with PBM (780 nm, Power: 100 mV, Power Density: 3.18 W/cm2, Energy: 4 J, Fluency: 127.4 J/cm2, Time: 40 s per point and 1.280 s total, Spot: 0.0314 cm2, 32 Points: 16 points (brachial biceps) and 16 points (brachial triceps) applied with contact at 90°, Total Energy: 64 J), which in the pre-treatment evaluation measured BL, the visual analogue scale (VAS) of pain; torque and EMG of the same muscles in the IC, subsequently, a new measurement of VAS and BL, and measurement of range of motion (ROM) during the reaching movement. At the conclusion of the ten sessions, all participants underwent a reassessment, wherein all tests originally administered during the initial evaluation were repeated. Subsequently, the data were analyzed using the Shapiro-Wilk normality test. For related data, the paired t-test was used for normal distributions and the Wilcoxon test for non-normal data. For unrelated data, the t test was used for normal distributions and the Mann-Whitney test for non-normal data. Muscle torque was higher for the CG, with a significant difference (CGxPBMG = p < 0.0001). There was no significant difference between the EMG values of the CG in relation to the Pre-PBM phase and with the Post-PBM phase of the PBMG (p > 0.05). On the other hand, there was a 38% reduction in pain reported by hemiparetic patients (p = 0.0127) and a decrease in BL in the PBMG. Post-PBM ROM increased by 46.1% in the elbow extension of the paretic limb. In conclusion, Photobiomodulation (PBM) demonstrated significant improvements in muscle performance, reducing fatigue and pain levels, and enhancing range of motion in post-stroke patients with spastic hemiparesis. These findings support the potential integration of PBM into rehabilitation protocols, but further research and clinical trials are needed to validate and expand upon these promising outcomes.

Transcranial photobiomodulation therapy associated with cardiorespiratory rehabilitation in spastic subjects.

The objective of this study was to evaluate the effects of cardiorespiratory rehabilitation (CR) and transcranial photobiomodulation (tPBM) on exercise tolerance (ET), heart rate variability (HRV), and peripheral muscle activity in individuals with spasticity. Fifteen participants with spasticity were randomly assigned to two groups: the tPBM group (tPBMG) consisted of eight volunteers who underwent tPBM (on mode) and CR, while the control group (CG) consisted of seven volunteers who underwent simulated tPBM (off mode) and CR. The CR program included 12 weeks of treatment, twice a week for one hour, involving aerobic exercises and lower limb strengthening. For tPBM, a cluster with three lasers (λ = 680 nm, 808 nm), with a power of 100 mW/laser and energy of 36 J, applied to the F7, F8, and Fpz points. The following parameters were evaluated after 8 and 12 weeks: ET, HRV, and surface electromyography (EMG) of the rectus femoris muscle during orthostasis (ORT), isometric squatting (ISOM), and isotonic squatting (ISOT). Both groups showed a 40% increase in ET for the CG and a 30% increase for the tPBMG. The CG had more pronounced parasympathetic modulation alterations during post-exercise effort and recovery compared to the tPBMG. The EMG results showed that the tPBMG exhibited progressive improvement in muscle activity during ISOM and ISOT, as well as a decrease in the interlimb difference. In conclusion, both CR and tPBMG demonstrated improvements in ET. However, tPBMG specifically showed promising effects on HRV modulation and peripheral muscle electrical activity, providing additional benefits compared to CR alone.

6-Nitrodopamine Is the Most Potent Endogenous Positive Inotropic Agent in the Isolated Rat Heart.

BACKGROUND: 6-nitrodopamine released from rat isolated atria exerts positive chronotropic action, being more potent than noradrenaline, adrenaline, and dopamine. Here, we determined whether 6-nitrodopamine is released from rat isolated ventricles (RIV) and modulates heart inotropism. METHODS: Catecholamines released from RIV were quantified by LC-MS/MS and their effects on heart inotropism were evaluated by measuring left ventricular developed pressure (LVDP) in Langendorff's preparation. RESULTS: 6-nitrodopamine was the major released catecholamine from RIV. Incubation with L-NAME (100 µM), but not with tetrodotoxin (1 µM), caused a significant reduction in 6-nitrodopamine basal release. 6-nitrodopamine release was significantly reduced in ventricles obtained from L-NAME chronically treated animals. 6-nitrodopamine (0.01 pmol) caused significant increases in LVDP and dP/dtmax, whereas dopamine and noradrenaline required 10 pmol, and adrenaline required 100 pmol, to induce similar increases in LVDP and dP/dtmax. The infusion of atenolol (10 nM) reduced basal LVDP and blocked the increases in LVDP induced by 6-ND (0.01 pmol), without affecting the increases in LVDP induced by 10 nmol of dopamine and noradrenaline and that induced by adrenaline (100 nmol). CONCLUSIONS: 6-nitrodopamine is the major catecholamine released from rat isolated ventricles. It is 1000 times more potent than dopamine and noradrenaline and is selectively blocked by atenolol, indicating that 6-ND is a main regulator of heart inotropism.

A phytotherapic blend immunity-6™ inhibits myeloid leukemic cells 2 activation involving purinergic signaling.

Leukemia is among the most common types of hematological cancers and the use of herbal medicines to prevent and treat leukemia are under quick development. Among several molecular pathways involved in leukemia pathogenesis and exacerbations, purinergic signaling is revealed as a key component. In the present study, the effects of two doses (5 ug/mL and 10 ug/mL) of Immunity-6™, a phytocomplex composed by beta-glucan, green tea (Camelia sinensis), chamomile (Matricaria chamomilla), and ascorbic acid (vitamin C) was tested in vitro, using chronic myelogenous leukemia cell line (K-562; 5 ×104/mL/well), which were challenged with lipopolysaccharide (LPS; 1 ug/mL) for 24 h. The results demonstrated that both doses of Immunity-6™ inhibited ATP release (p < 0.001) and P2×7 receptor at mRNA levels expression (p < 0.001). Purinergic inhibition by Immunity-6™ was followed by reduced release of proinflammatory cytokines IL-1beta (p < 0.001) and IL-6 (p < 0.001), while only 5 ug/mL of Immunity-6™ reduced the release of TNF-alpha (p < 0.001). Beyond to inhibit the release of pro-inflammatory cytokines, both doses of Immunity-6™ induced the release of anti-inflammatory cytokine IL-10 (p < 0.001), while only the higher dose (10 ug/mL) of Immunity-6™ induced the release of anti-inflammatory IL-1ra (p < 0.05) and klotho (p < 0.001). Thus, Immunity-6™ may be a promising adjuvant in the treatment of leukemia and further clinical trials are guaranteed.

Combined resistance and aerobic training improves lung function and mechanics and fibrotic biomarkers in overweight and obese women.

Background: Obesity impairs lung function and mechanics and leads to low-grade inflammation, but the effects of combined physical exercise (CPE) on that are unknown. Methods: We investigated the effects of 12 weeks of combined physical exercise (aerobic + resistance training), in non-obese (n = 12), overweight (n = 17), and obese grade I (n = 11) women. Lung function and lung mechanics were evaluated. The systemic immune response was evaluated by whole blood analysis and biomarker measurements, while pulmonary fibrotic biomarkers were evaluated in the breath condensate. Result: CPE improved forced vital capacity (FVC) % (p < 0.001) and peak expiratory flow (PEF) % (p < 0.0003) in the obese group; resistance of the respiratory system (R5Hz) in non-obese (p < 0.0099), overweight (p < 0.0005), and obese (p < 0.0001) groups; resistance of proximal airways (R20Hz) in non-obese (p < 0.01), overweight (p < 0.0009), and obese (p < 0.0001) groups; resistance of distal airways (R5Hz-R20Hz) in non-obese (p < 0.01), overweight (p < 0.0012), and obese (p < 0.0001) groups; reactance of the respiratory system (X5Hz) in non-obese (p < 0.01), overweight (p < 0.0006), and obese (p < 0.0005) groups; impedance of the respiratory system (Z5Hz) in non-obese (p < 0.0099), overweight (p < 0.0005), and obese (p < 0.0001) groups; central resistance (RCentral) in non-obese (p < 0.01), overweight (p < 0.001), and obese (p < 0.0003) groups; and the peripheral resistance (RPeripheral) in non-obese (p < 0.03), overweight (p < 0.001), and obese (p < 0.0002) groups. CPE reduced the pro-fibrotic IGF-1 levels in BC in overweight (p < 0.0094) and obese groups (p < 0.0001) and increased anti-fibrotic Klotho levels in BC in obese (p < 0.0001) groups, and reduced levels of exhaled nitric oxide in overweight (p < 0.03) and obese (p < 0.0001) groups. Conclusion: CPE improves lung function, mechanics, and pulmonary immune response in overweight and obese grade I women by increasing anti-fibrotic protein Klotho and reducing pro-fibrotic IGF-1.

Efficacy of low-level laser therapy in patients with lower extremity tendinopathy or plantar fasciitis: systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: We investigated the effectiveness of low-level laser therapy (LLLT) in lower extremity tendinopathy and plantar fasciitis on patient-reported pain and disability. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Eligible articles in any language were identified through PubMed, Embase and Physiotherapy Evidence Database (PEDro) on the 20 August 2020, references, citations and experts. ELIGIBILITY CRITERIA FOR SELECTION OF STUDIES: Only randomised controlled trials involving participants with lower extremity tendinopathy or plantar fasciitis treated with LLLT were included. DATA EXTRACTION AND SYNTHESIS: Random effects meta-analyses with dose subgroups based on the World Association for Laser Therapy treatment recommendations were conducted. Risk of bias was assessed with the PEDro scale. RESULTS: LLLT was compared with placebo (10 trials), other interventions (5 trials) and as an add-on intervention (3 trials). The study quality was moderate to high.Overall, pain was significantly reduced by LLLT at completed therapy (13.15 mm Visual Analogue Scale (VAS; 95% CI 7.82 to 18.48)) and 4-12 weeks later (12.56 mm VAS (95% CI 5.69 to 19.42)). Overall, disability was significantly reduced by LLLT at completed therapy (Standardised Mean Difference (SMD)=0.39 (95% CI 0.09 to 0.7) and 4-9 weeks later (SMD=0.32 (95% CI 0.05 to 0.59)). Compared with placebo control, the recommended doses significantly reduced pain at completed therapy (14.98 mm VAS (95% CI 3.74 to 26.22)) and 4-8 weeks later (14.00 mm VAS (95% CI 2.81 to 25.19)). The recommended doses significantly reduced pain as an add-on to exercise therapy versus exercise therapy alone at completed therapy (18.15 mm VAS (95% CI 10.55 to 25.76)) and 4-9 weeks later (15.90 mm VAS (95% CI 2.3 to 29.51)). No adverse events were reported. CONCLUSION: LLLT significantly reduces pain and disability in lower extremity tendinopathy and plantar fasciitis in the short and medium term. Long-term data were not available. Some uncertainty about the effect size remains due to wide CIs and lack of large trials. PROSPERO REGISTRATION NUMBER: CRD42017077511.

Efficacy of prolonged application of low-level laser therapy combined with exercise in knee osteoarthritis: A randomized controlled double-blind study.

OBJECTIVES: To investigate the effect of prolonged low-level laser therapy application combined with exercise on pain and disability in patients with osteoarthritis of the knee. DESIGN: A randomized controlled trial. SETTING: Special rehabilitation services. SUBJECTS: Forty-three participants with knee osteoarthritis. INTERVENTION: Following initial assessment, participants were randomly allocated to the Laser group (n = 22, 44 knees) and received low-level laser therapy while the Placebo group (n = 21, 42 knees) received placebo therapy three times a week for 3 weeks. Both groups then received low-level laser therapy combined with exercise three times a week for the following 8 weeks. MAIN OUTCOME MEASURES: The primary outcome was change in knee pain and disability (Lequesne). Secondary outcomes included change in mobility (Timed Up and Go test), range of motion (goniometer), muscular strength (dynamometer), activity (Western Ontario and McMaster Universities Osteoarthritis questionnaire), and medication intake and relief. RESULTS: Mean (SD) age of participants was 63.02 (9.9) years. Pain scores at baseline, 3 weeks, 11 weeks, and 6 months follow-up were 9.1 (1.3), 2.6 (2.3), 0.2 (0.9), and 0.2 (0.8) for the Laser group and 9.5 (8.0), 7.7 (5.3), 5.6 (2.4), and 7.4 (5.0) for the Placebo group, respectively. Disability scores at baseline, 3 weeks, 11 weeks, and 6 months follow-up were 14.9 (4.7), 7.6 (4.8), 3.9 (4.2), and 3.5 (4.1) for the Laser group and 17.8 (14.7), 15.2 (11.5), 11.6 (6.4), and 15.8 (11.9) for the Placebo Group, respectively. CONCLUSION: In participants with osteoarthritis of the knee, the isolated application of low-level laser therapy in the initial 3 weeks and combined with exercises in the final 8 weeks reduced pain, disability, and intake of medication over a 6-month period.

Short- and Long-Term Effectiveness of Low-Level Laser Therapy Combined with Strength Training in Knee Osteoarthritis: A Randomized Placebo-Controlled Trial.

BACKGROUND: Both physical activity and low-level laser therapy (LLLT) can reduce knee osteoarthritis (KOA) inflammation. We conducted a randomized clinical trial to investigate the short- and long-term effectiveness of LLLT combined with strength training in persons with KOA. METHODS: Fifty participants were randomly divided in two groups, one with LLLT plus strength training (n = 26) and one with placebo LLLT plus strength training (n = 24). LLLT and strength training were performed triweekly for 3 and 8 weeks, respectively. In the laser group, 3 joules 904 nm wavelength laser was applied to fifteen points (45 joules) per knee per session. Patient-reported outcomes, physical tests, and ultrasonography assessments were performed at baseline and 3, 8, 26, and 52 weeks after initial LLLT or placebo therapy. The primary outcomes were pain on movement, at rest, at night (Visual Analogue Scale), and globally (Knee injury and Osteoarthritis Outcome Score (KOOS) subscale). Parametric data were assessed with analysis of variance using Sidák's correction. RESULTS: There were no significant between-group differences in the primary outcomes. However, in the laser group there was a significantly reduced number of participants using analgesic and non-steroidal anti-inflammatory drugs and increased performance in the sit-to-stand test versus placebo-control at week 52. The joint line pain pressure threshold (PPT) improved more in the placebo group than in the laser group, but only significantly at week 8. No other significant treatment effects were present. However, pain on movement and joint line PPT were worse in the placebo group at baseline, and therefore, it had more room for improvement. The short-term percentage of improvement in the placebo group was much higher than in similar trials. CONCLUSIONS: Pain was reduced substantially in both groups. LLLT seemed to provide a positive add-on effect in the follow-up period in terms of reduced pain medication usage and increased performance in the sit-to-stand test.

Improved Spatial Memory And Neuroinflammatory Profile Changes in Aged Rats Submitted to Photobiomodulation Therapy.

Recent evidences have shown the therapeutic potential of transcranial photobiomodulation on traumatic brain injury and Alzheimer's disease. Despite the promising benefits in the brain, little is known about the laser's effects in the absence of pathological conditions. We submitted young (4 months old) and aged (20 months old) rats to transcranial low-level laser and evaluated their exploratory activity and habituation in open field, anxiety in elevated plus maze, spatial memory in Barnes maze, and aversive memory in a step-down inhibitory avoidance task. Additionally, the levels of a panel of inflammatory cytokines and chemokines were quantified in two different brain regions: the cerebral cortex and the hippocampus. Young and aged rats submitted to transcranial laser exhibited better cognitive performance in Barnes maze than did control rats. Transcranial laser therapy decreased cortical levels of GM-CSF, IL-10, MCP-1, LIX, and TNFα in young rats and IL-5 in aged rats. High levels of IL-6, IL-10, and TNF-alpha were found in the cerebral cortex of aged rats submitted to transcranial laser. In the hippocampus, a decrease in IP-10 and fractalkine levels was observed in the aged rats from the laser group when compared to the aged rats from the control group. Our data indicate that transcranial photobiomodulation improves spatial learning and memory and alters the neuroinflammatory profile of young and aged rats' brains.

Transcranial Laser Photobiomodulation Improves Intracellular Signaling Linked to Cell Survival, Memory and Glucose Metabolism in the Aged Brain: A Preliminary Study.

Aging is often accompanied by exacerbated activation of cell death-related signaling pathways and decreased energy metabolism. We hypothesized that transcranial near-infrared laser may increase intracellular signaling pathways beneficial to aging brains, such as those that regulate brain cell proliferation, apoptosis, and energy metabolism. To test this hypothesis, we investigated the expression and activation of intracellular signaling proteins in the cerebral cortex and hippocampus of aged rats (20 months old) treated with the transcranial near-infrared laser for 58 consecutive days. As compared to sham controls, transcranial laser treatment increased intracellular signaling proteins related to cell proliferation and cell survival, such as signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p70 ribosomal protein S6 kinase (p70S6K) and protein kinase B (PKB), also known as Akt that is linked to glucose metabolism. In addition, ERK is linked to memory, while ERK and JNK signaling pathways regulate glucose metabolism. Specifically, the laser treatment caused the activation of STAT3, ERK, and JNK signaling proteins in the cerebral cortex. In the hippocampus, the laser treatment increased the expression of p70S6K and STAT3 and the activation of Akt. Taken together, the data support the hypothesis that transcranial laser photobiomodulation improves intracellular signaling pathways linked to cell survival, memory, and glucose metabolism in the brain of aged rats.

The influence of photobiomodulation on the temperature of the brachial biceps during muscle fatigue protocol.

Physical activity raises body temperature. However, the literature does not contain studies about whether the employment of hotobiomodulation (PMB) could significantly influence body temperature during a muscle fatigue (MF) protocol. Thus, the aim of this study was to evaluate the effects of PMB on the temperature of the biceps brachii muscle during the performance of a muscle fatigue protocol. The study consisted of 14 volunteers who were divided into two groups (placebo group and laser group) and all individuals rotated into all groups (crossover study). To induce muscle fatigue, three maximum voluntary isometric contractions (MVIC) were performed for 50 s with a 50-s interval. During the MVIC, the muscle strength was assessed using surface electromyography and infrared temperature at 0, 5, 10, and 15 min after the tests. The laser group presented a less accentuated decrease in muscle strength, evidencing a lower rate of muscle fatigue (p > 0.05) in relation to the other groups. In the temperature analysis, the control group exhibited the highest average temperature, with a significant difference only for the placebo. The results indicate that the control displayed the greatest physical degeneration and the PMB group had a positive effect on MF attenuation and body thermoregulation.

Effectiveness of Low-Level Laser Therapy Associated with Strength Training in Knee Osteoarthritis: Protocol for a Randomized Placebo-Controlled Trial.

Physical activity and low-level laser therapy (LLLT) can reduce knee osteoarthritis (KOA) inflammation. We are conducting a randomized placebo-controlled trial to investigate the long-term effectiveness of LLLT combined with strength training (ST) in persons with KOA, since it, to our knowledge, has not been investigated before. Fifty participants were enrolled. LLLT and ST was performed 3 times per week over 3 and 8 weeks, respectively. In the LLLT group, 3 Joules of 904 nm wavelength laser was applied to 15 spots per knee (45 Joules/knee/session). The primary outcomes are pain during movement, at night and at rest (Visual Analogue Scale) and global pain (Knee injury and Osteoarthritis Outcome Score, KOOS) pain subscale. The secondary outcomes are KOOS disability and quality-of-life, analgesic usage, global health change, knee active range of motion, 30 s chair stand, maximum painless isometric knee extension strength, knee pain pressure threshold and real-time ultrasonography-assessed suprapatellar effusion, meniscal neovascularization and femur cartilage thickness. All the outcomes are assessed 0, 3, 8, 26 and 52 weeks post-randomization, except for global health change, which is only evaluated at completed ST. This study features the blinding of participants, assessors and therapists, and will improve our understanding of what occurs with the local pathophysiology, tissue morphology and clinical status of persons with KOA up to a year after the initiation of ST and a higher 904 nm LLLT dose than in any published trial on this topic.

Quantification of 6-nitrodopamine in Krebs-Henseleit's solution by LC-MS/MS for the assessment of its basal release from Chelonoidis carbonaria aortae in vitro.

In this study, the development and validation of a method for quantification of 6-nitrodopamine in Krebs-Henseleit's solution by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with positive ion electrospray ionization is described. Aortic rings taken from tortoise were either denuded or left with endothelium intact (15 mm, N = 6) and were incubated for 30 min in 5 mL Krebs-Henseleit's solution in an organ bath. Solid phase extraction (SPE) was performed for aliquots of 1 mL of the supernatant. The separation of 6-nitrodopamine was obtained on a 150 mm × 3 mm Shim-pack GIST-HP C18 column, using 75% of mobile phase A consisted of deionized water with 0.1% formic acid (v/v) and 25% of mobile phase B consisted of acetonitrile/deionized water (50/50, v/v) + 0.1% formic acid at a flow rate of 350 µL/min in an isocratic mode. The method was linear over the concentration range of 0.1-20 ng/mL. The method was sensitive, precise and accurate for the assessment of the basal release of 6-nitrodopamine from Chelonoidis carbonaria aortae in vitro. The mean ± SEM concentrations of 6-nitrodopamine released from endothelium-intact and endothelium-denuded aortae were 0.44 ± 0.06 ng/mL and 0.18 ± 0.05 ng/mL, respectively. These results indicate that tortoise's aortae display a basal endothelium-derived 6-nitrodopamine release.

Effects of Chronic Photobiomodulation with Transcranial Near-Infrared Laser on Brain Metabolomics of Young and Aged Rats.

Since laser photobiomodulation has been found to enhance brain energy metabolism and cognition, we conducted the first metabolomics study to systematically analyze the metabolites modified by brain photobiomodulation. Aging is often accompanied by cognitive decline and susceptibility to neurodegeneration, including deficits in brain energy metabolism and increased susceptibility of nerve cells to oxidative stress. Changes in oxidative stress and energetic homeostasis increase neuronal vulnerability, as observed in diseases related to brain aging. We evaluated and compared the cortical and hippocampal metabolic pathways of young (4 months old) and aged (20 months old) control rats with those of rats exposed to transcranial near-infrared laser over 58 consecutive days. Statistical analyses of the brain metabolomics data indicated that chronic transcranial photobiomodulation (1) significantly enhances the metabolic pathways of young rats, particularly for excitatory neurotransmission and oxidative metabolism, and (2) restores the altered metabolic pathways of aged rats towards levels found in younger rats, mainly in the cerebral cortex. These novel metabolomics findings may help complement other laser-induced neurocognitive, neuroprotective, anti-inflammatory, and antioxidant effects described in the literature.

Photobiomodulation Therapy Modulates Muscle Gene Expression and Improves Performance of Rats Subjected to a Chronic Resistance Exercise Protocol.

Objective: In professional sports activities, the search for increased performance is constant. Electrophysical agents, including photobiomodulation (PBM), have been used in the sports context to accelerate postworkout recovery, prevent injuries, and even to improve performance. This study aims to investigate the effects of infrared laser (904 nm) on skeletal muscle gene expression of performance-related proteins of rats submitted to a chronic resistance training protocol. Materials and methods: Male Wistar rats (n = 40), weighing ±300 g were divided into four groups: sedentary control (CT, n = 10); irradiated control (CTL, n = 10); exercised not irradiated (EX, n = 10); exercised irradiated (EXL, n = 10). To assess the performance, the maximum carrying test was adapted and applied 72 h prior the training and 72 h after the last exercise session. The vertical weight climbing protocol was adapted for resistance training 3 × per week with 48 h interval between each session: first week adaptation, second week 25% of body weight (BW), third week 50% BW, fourth week 75% BW, and fifth week 100% BW. Animals were irradiated before exercise on hind paws 50 sec each, with infrared laser 904 nm 5 days per week, during 4 weeks, 9 J per leg in a total of 18 J energy per day. Results: The EXL performed more climbing (7.1 ± 0.91) compared to EX (4.4 ± 0.63). PBM promoted increased expression of lactate dehydrogenase enzyme, mammalian target of rapamycin protein, and androgen receptor (p < 0.05) but not the myosin heavy chain (p = 0.43). Conclusions: PBM therapy increases the expression of performance-related muscle mass gain genes besides improving the resistance training performance.

Effect of 12 Weeks of Endurance Training Combined with Creatine Supplement, Photobiomodulation Therapy, or Both on Performance and Muscle Damage in Rats.

Background: Photobiomodulation therapy (PBMT) and creatine (Cr) intake have been used in conjunction with heavy training, but little is known about their possible effects during a long-term training program. Objective: We assessed long-term use of PBMT and Cr in an exercise training program. Methods: Twenty-five male Wistar rats weighing ∼300 g were randomly allocated to one of five groups: a nontraining control group, a training group, a training group receiving Cr, a training group receiving PBMT, and a training group receiving both PBMT and Cr. The training program consisted of 12 weeks of daily swimming training. PBMT was delivered in six points with a laser device (808 nm, 100 mW, 30 sec per point of irradiation, 3 J, 75 J/cm2). Results: All training groups showed significantly higher peak force and longer time to 50% decay of force, and lower creatine kinase (CK) levels than the nontraining control group, thus confirming the benefit of the training program. In all outcomes related to muscle performance, the groups receiving PBMT with or without Cr supplement performed significantly better (p < 0.05) peak force and time of force decay during an electrical stimulation protocol than all the other groups. In addition, CK levels were also significantly lower for the PBMT groups than for the other groups. Conclusions: We conclude that PBMT alone or in conjunction with Cr supplement during a 12-week training program resulted in significantly better muscle performance and lower levels of CK, a biochemical marker of muscle damage.

Therapeutic Potential of Photobiomodulation In Alzheimer's Disease: A Systematic Review.

Introduction: Alzheimer disease (AD) is characterized by the decline of cognitive functions such as learning and memory. Scientific society has proposed some non-pharmacological interventions, among which photobiomodulation has gained prominence for its beneficial effects. Therefore, we investigated, through systematic review, the therapeutic potential of photobiomodulation in AD. Methods: This systematic review was registered under the number CRD42019128416 in the International Prospective Record of Systematic Reviews (PROSPERO). A systematic search was conducted on the bibliographic databases (PubMed and ScienceDirect) with the keywords based on MeSH terms: "photobiomodulation therapy" or "low-level laser therapy" or "LLLT" or "light emitting diode" and "amyloid" or "Alzheimer". The data search was conducted from 2008 to 2019. We follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The search strategy included experimental in vivo and in vitro studies in the English language and photobiomodulation as a non-pharmacological intervention. We included 10 studies, being 5 in vivo studies, 4 in vitro studies and 1 study using in vivo and in vitro. To evaluate the quality of the studies, we used the Rob tool of the Systematic Review Center for Laboratory Animal Experimentation (SYRLE). Results: The studies showed that photobiomodulation is able to reduce inflammatory response, oxidative stress and apoptotic effects generated by amyloid beta (Aß) and restore mitochondrial function and cognitive behavior. Conclusion: Taken together, these results indicate that photobiomodulation may be a useful tool for treating AD.

904 nm Low-Level Laser Irradiation Decreases Expression of Catabolism-Related Genes in White Adipose Tissue of Wistar Rats: Possible Roles of Laser on Metabolism.

Background: Adipose tissue is the main energy storage tissue in the body. Its catabolic and anabolic responses depend on several factors, such as nutritional status, metabolic profile, and hormonal signaling. There are few studies addressing the effects of laser photobiomodulation (PBM) on adipose tissue and results are controversial. Objective: Our purpose was to investigate the metabolic effects of PBM on adipose tissue from Wistar rats supplemented or not with caffeine. Materials and methods: Wistar rats were divided into four groups: control (CTL), laser-treated [CTL (L)], caffeine (CAF), and caffeine+PBM [CAF (L)]. Blood was extracted for quantification of triglyceride and cholesterol levels and white adipose tissues were collected for analysis. We evaluated gene expression in the adipose tissue for the leptin receptor, lipase-sensitive hormone, tumor necrosis factor alpha, and beta adrenergic receptor. Results: We demonstrated that the low-level laser irradiation was able to increase the feed intake of the animals and the relative mass of the adipose tissue in the CTL (L) group compared with CTL. Laser treatment also increases serum triglycerides [CTL = 46.99 ± 5.87; CTL (L) = 57.46 ± 14.38; CAF = 43.98 ± 5.17; and CAF (L) = 56.9 ± 6.12; p = 0.007] and total cholesterol (CTL = 70.62 ± 6.80; CTL (L) = 79.41 ± 13.07; CAF = 71.01 ± 5.52; and CAF (L) = 79.23 ± 6.881; p = 0.003). Conclusions: Laser PBM decreased gene expression of the studied genes in the adipose tissue, indicating that PBM is able to block the catabolic responses of this tissue. Interestingly, the CAF (L) and CAF animals presented the same CLT (L) phenotype, however, without increasing the feed intake and the relative weight of the adipose tissue. The description of these phenomena opens a new perspective for the study of the action of low-level laser in adipose tissue.

Comparative bioavailability of two zolpidem hemitartrate formulations in healthy human Brazilian volunteers using high-performance liquid chromatography coupled to tandem mass spectrometry.

To assess the bioequivalence of two zolpidem hemitartrate formulations in 30 healthy volunteers. Plasma samples were obtained over a 24 h period. Plasma concentrations of zolpidem were analyzed by liquid chromatography coupled to tandem mass spectrometry with positive ion electrospray ionization using multiple reaction monitoring. Values of peak concentration (Cmax ), area under curve (AUC), half-life, elimination constant, volume of distribution and clearance showed statistically significant differences when comparing women (604.34 ng h/ml, 127.36 ng/ml, 4.4 h, 0.18 1/h, 50.56 L and 8.55 L/h, respectively) and men (276.1 ng h/ml, 70.9 ng/ml, 3.3 h, 0.26 1/h, 91.42 L and 24.34 L/h, respectively), receiving the same dose (5 mg), respectively. The geometric means with corresponding 90% confidence interval for Test/Reference percentage ratios were 99.73% (CI 93.69-106.16) for Cmax, 97.44% (90% CI = 91.85-103.37%) for area under curve of plasma concentration until the last concentration observed (AUClast ) and 98.30% (90% CI = 92.48-104.49) for the area under curve between the first sample (pre-dosage) and infinity (AUC0-inf ). Since the 90% CI for AUClast , AUC0-inf and Cmax ratios were within the 80-125% interval proposed by the US Food and Drug Administration, it was concluded that zolpidem hemitartrate formulation (5 mg orodispersible tablet) is bioequivalent to the zolpidem hemitartrate formulation (Patz SL 5 mg sublingual tablet) with regard to both the rate and the extent of absorption. A new formulation of zolpidem 2.5 mg may be useful in women for the same clinical benefits as the 5 mg formulation in men.